Generation gains (Nonesuch autumn 2014)

5 November 2014

As many of the babies born into the University’s Children of the 90s project branch out into adulthood, the future looks rosy for one of the largest long-term
health population studies in the world. And with almost 26,000 participants, it’s still growing.

Health, development and behaviour differ markedly between individuals, but how much of this variation is down to our genes, and how much is influenced by our environment? Teasing out the complex relationships between genes and environmental factors, and how they interact over time to affect health and development, is extremely difficult and requires huge amounts of data, collected over many years, for researchers to study. Enter the Children of the 90s project, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC).

First steps

Jean Golding OBE (Hon LLD 2013), Emeritus Professor of Paediatric and Perinatal Epidemiology, founded ALSPAC in 1990. It was not the first long-term population study in the UK, but Golding believed that existing studies were too narrowly defined by participants’ birth dates, and that many factors influencing health and development were linked to mothers’ behaviour and lifestyleduring pregnancy, if not earlier.

ALSPAC broke new ground by recruiting pregnant women so that researchers could gather detailed information on the babies’ parents and grandparents that might affect the children’s lives even before they were born.

Great leap forward

Another distinctive feature of the study was the breadth of the data collected. Genetics was in its infancy in the early ’90s (Golding recalls funders’ eyes ‘glazing over’ at the very mention of the word), but, encouraged by leading clinical geneticist Professor Marcus Pembrey, the ALSPAC team was determined to give the study a genetic component.

'Received wisdom among scientists at the time was that research should focus on a specific outcome, say, asthma, dyslexia or depression,' says Golding. 'Our approach was more holistic; we wanted to look at how family background, behaviours and genes work together to affect children’s overall development, and whether – and why – they remain healthy or become ill.'

And so ALSPAC became the first longitudinal study to collect biological samples from participants, including urine, hair, blood and DNA. This data was to be analysed alongside detailed records of characteristics such as diet, lifestyle, socioeconomic status and emotional health.

The long haul

Golding’s team was committed to maintaining the project’s momentum by continually collecting information. And it succeeded. More than 14,000 pregnant women in Bristol and the surrounding area signed up to the project in 1991 and 1992, many of whom still participate, along with 8,000 children, 3,000 dads, 200 ‘children of the children’ and 550 siblings.

Researchers are now in the process of recruiting the parents of the original mothers and fathers. If enough grandparents participate, ALSPAC will be in the unique position of being able to provide genetic information for up to four generations of the same family. And as its participants are its most valuable asset, ALSPAC is also involving some of its enthusiastic contributors in decisions about how the study might evolve in the future.

Future investment

Today ALSPAC, headed by Professor George Davey Smith, a dedicated team member for the past ten years, and newcomer Professor Paul Burton, is in rude health. Its unrivalled bank of data and repository of biosamples have made it a world-leading research platform for scientists around the world. The project is maturing in a world characterised by rapid advances in biotechnology. Researchers using the study have a key focus on the emerging field of epigenetics – the interaction between genes and the environment during development, whereby external factors turn genes on or off.

Scientists are beginning to use epigenetic information to predict disease and target treatment, as well as develop new medicines, with some of the most exciting work in this area being carried out at the University’s MRC Integrative Epidemiology Unit, also directed by Davey Smith.

ALSPAC is also benefitting from increasingly sophisticated use of data. Cutting-edge information systems and anonymisation now enable researchers to align ALSPAC data with information fromprimary care records and to analyse data alongside that of other cohort studies.

Burton feels privileged to be involved in a project widely seen as an exemplar of the best in contemporary health and social science, thanks to the work of Golding, Davey Smith and, of course, the participants. He has arrived in the year that has seen the publication of the 1,000th academic paper based on ALSPAC data – 'by any standards a prodigious rate of return on the funding invested in it,' he says.

He’s not the only one to think so: the project recently received almost £8 million from the Medical Research Council and the Wellcome Trust to continue its work until March 2019. As Golding attests: ‘No other study has anything like the same amount of detail and potential to answer questions, and it will get more and more valuable as time goes on.’ ALSPAC’s ‘bank of life’ is set topay dividends for generations to come.

Living history

Bristol student Stephen Hardman (BSc 2014, Medicine 2014-) and alumna Kim Mather (LLB 2013), two of the original Children of the 90s participants, reflect on what it means to be part of the study.

Steve

From the age of about nine I was curious about why I was going to the clinic for all these tests. Some people struggle with the fact that you don’t see immediate results with this kind of study but studying medicine helps put it into context. It’s fascinating to be part of a scientific process – I am the data and I can see how the data is used to advance our knowledge.

The work on epigenetics is particularly interesting – the idea that the way our DNA is expressed could predispose us to diseases later in life, depending on whether, say, our mother was a smoker when we were still in the womb. ALSPAC has helped lay the foundations for research in this field.

I intend to stick with the study. My brothers are joining, as siblings are now being included. The sheer volume of the data means that researchers can eliminate a significant amount of bias that might invalidate results.

I already have a degree in Biochemistry and I’m interested in developing treatments for hypoxic-ischaemic brain injuries, where the brain is deprived of oxygen, for example in strokes.

Whatever I do, I know what it’s like to be on the receiving end of a blood test or to lie in a brain scanner for several hours, though I’m lucky enough not to have been there because of illness. I hope this experience will help make me a better doctor.

Kim

I first became aware of being in the study when I caught my mum taking a tooth that I’d hidden for the tooth fairy. She confessed to collecting my milk teeth for the Children of the 90sresearchers.

I used to look forward to going into the clinic. The tests were fun – and I got the day off school! There were quite a few other participants in my year and it felt like we were part of something special. Our other friends thought we were cool.

It’s a bit of a family affair now. My step-dad and sister are taking part, and my daughter Annie, who’s five, is part of the COCO90s group – the Children of the Children of the 90s. It’s intriguing to see her doing all these tests that I did at that age. It’s given me a better understanding of child development.

It’s amazing that, for a small amount of effort by individual participants, so much has been discovered. It’s great that there are simple things you can do to have a healthier baby, like eating oily fish when you’re pregnant.

Taking part in the study has increased my sense of belonging to the community. Bristol has always had what I wanted – the right degree at the right university, in the right city. I’ve just got a teaching qualification and have started work in a local school, so it looks like I'm here to stay.